scholarly journals SIRT1 Attenuates Kidney Disorders in Male Offspring Due to Maternal High-Fat Diet

Nutrients ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 146 ◽  
Author(s):  
Long Nguyen ◽  
Crystal Mak ◽  
Hui Chen ◽  
Amgad Zaky ◽  
Muh Wong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Responses ◽  
High Fat Diet ◽  
Maternal Obesity ◽  
Metabolic Stress ◽  
Kidney Injury ◽  
Male Offspring ◽  
High Fat ◽  
Obese Female ◽  
Chronic Kidney Injury

Maternal obesity has been associated with kidney disorders in male offspring. Our previous studies have demonstrated that Sirtuin (SIRT)1, an essential regulator of metabolic stress responses, is suppressed in the offspring as the result of maternal high-fat diet (HFD) consumption, which is likely to underpin the adverse metabolic and renal outcomes. To examine if SIRT1 overexpression or activation early in life can protect the offspring kidney, wild-type (WT) and transgenic (Tg) offspring were born to the same diet-induced obese female C57BL/6 mice through breeding with hemizygous SIRT1-transgenic (Tg) male mice and examined for renal pathological changes. In separate experiments, SIRT1 activator SRT1720 (25 mg/kg/2 days i.p) was administrated in WT offspring over 6 weeks of postnatal high-fat diet exposure. The results show that offspring born to obese dams have increased kidney weight, higher levels of renal triglycerides, and increased expression of oxidative stress, inflammatory, and fibrotic markers, as well as increased albuminuria compared to offspring of control dams. Both SIRT1 overexpression and SRT1720 treatment attenuated renal lipid contents and expression of lipogenesis, oxidative stress, and inflammatory markers; however, fibrosis was modestly reduced and albuminuria was not affected. The findings suggest that SIRT1 therapy can ameliorate some pathological mechanisms of kidney programming due to maternal obesity but may not be sufficient to prevent the resulting chronic kidney injury.

scholarly journals Maternal high-fat diet induces metabolic stress response disorders in offspring hypothalamus

2017 ◽  
Vol 59 (1) ◽  
pp. 81-92 ◽  
Author(s):  
Long The Nguyen ◽  
Sonia Saad ◽  
Yi Tan ◽  
Carol Pollock ◽  
Hui Chen
Keyword(s):  
Endoplasmic Reticulum ◽  
Body Weight ◽  
Er Stress ◽  
High Fat Diet ◽  
Maternal Obesity ◽  
Mrna Level ◽  
Metabolic Stress ◽  
High Fat ◽  
Chemical Chaperone ◽  
Protein Levels

Maternal obesity has been shown to increase the risk of obesity and related disorders in the offspring, which has been partially attributed to changes of appetite regulators in the offspring hypothalamus. On the other hand, endoplasmic reticulum (ER) stress and autophagy have been implicated in hypothalamic neuropeptide dysregulation, thus may also play important roles in such transgenerational effect. In this study, we show that offspring born to high-fat diet-fed dams showed significantly increased body weight and glucose intolerance, adiposity and plasma triglyceride level at weaning. Hypothalamic mRNA level of the orexigenic neuropeptide Y (NPY) was increased, while the levels of the anorexigenic pro-opiomelanocortin (POMC), NPY1 receptor (NPY1R) and melanocortin-4 receptor (MC4R) were significantly downregulated. In association, the expression of unfolded protein response (UPR) markers including glucose-regulated protein (GRP)94 and endoplasmic reticulum DNA J domain-containing protein (Erdj)4 was reduced. By contrast, protein levels of autophagy-related genes Atg5 and Atg7, as well as mitophagy marker Parkin, were slightly increased. The administration of 4-phenyl butyrate (PBA), a chemical chaperone of protein folding and UPR activator, in the offspring from postnatal day 4 significantly reduced their body weight, fat deposition, which were in association with increased activating transcription factor (ATF)4, immunoglobulin-binding protein (BiP) and Erdj4 mRNA as well as reduced Parkin, PTEN-induced putative kinase (PINK)1 and dynamin-related protein (Drp)1 protein expression levels. These results suggest that hypothalamic ER stress and mitophagy are among the regulatory factors of offspring metabolic changes due to maternal obesity.

scholarly journals Sesamin Ameliorates High-Fat Diet–Induced Dyslipidemia and Kidney Injury by Reducing Oxidative Stress

Nutrients ◽  
2016 ◽  
Vol 8 (5) ◽  
pp. 276 ◽  
Author(s):  
Ruijuan Zhang ◽  
Yan Yu ◽  
Jianjun Deng ◽  
Chao Zhang ◽  
Jinghua Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Fat Diet ◽  
Kidney Injury ◽  
High Fat

scholarly journals Extraction and Hypolipidemic Activity of Low Molecular Weight Polysaccharides Isolated from Rosa Laevigata Fruits

2020 ◽  
Vol 2020 ◽  
pp. 1-20
Author(s):  
Xuejiao Zhang ◽  
Yihong Hu ◽  
Chenzhong Jin ◽  
Weiguo Wu
Keyword(s):  
Oxidative Stress ◽  
Molecular Weight ◽  
Stress Responses ◽  
High Fat Diet ◽  
Raw Material ◽  
Low Molecular Weight ◽  
Peroxisome Proliferator ◽  
Extraction Temperature ◽  
High Fat ◽  
Chinese Medicinal Herb

Three novel low molecular weight polysaccharides (RLP-1a, RLP-2a, and RLP-3a) with 9004, 8761, and 7571 Da were first obtained by purifying the crude polysaccharides from the fruits of a traditional Chinese medicinal herb Rosae Laevigatae. The conditions for polysaccharides from the R. Laevigatae fruit (RLP) extraction were optimized by the response surface methodology, and the optimal conditions were as follows: extraction temperature, 93°C; extraction time, 2.8 h; water to raw material ratio, 22; extraction frequency, 3. Structural characterization showed that RLP-1a consisted of rhamnose, arabinose, xylose, glucose, and galactose with the ratio of 3.14 : 8.21 : 1 : 1.37 : 4.90, whereas RLP-2a was composed of rhamnose, mannose, glucose, and galactose with the ratio of 1.70 : 1 : 93.59 : 2.73, and RLP-3a was composed of rhamnose, arabinose, xylose, mannose, glucose, and galactose with the ratio of 6.04 : 26.51 : 2.05 : 1 : 3.17 : 31.77. The NMR analyses revealed that RLP-1a, RLP-2a, and RLP-3a contained 6, 4, and 6 types of glycosidic linkages, respectively. RLP-1a and RLP-3a exhibited distinct antioxidant abilities on the superoxide anions, 1,1-diphenyl-2-picrylhydrazyl (DPPH), and hydroxyl radicals in vitro. RLPs could decrease the serum lipid levels, elevate the serum high-density lipoprotein cholesterol levels, enhance the antioxidant enzymes levels, and upregulate of FADS2, ACOX3, and SCD-1 which involved in the lipid metabolic processes and oxidative stress in the high-fat diet-induced rats. These results suggested that RLPs ameliorated the high-fat diet- (HFD-) induced lipid metabolism disturbance in the rat liver through the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Low molecular weight polysaccharides of RLP could be served as a novel potential functional food for improving hyperlipidemia and liver oxidative stress responses.

scholarly journals Changes in Melanocortin Expression and Inflammatory Pathways in Fetal Offspring of Nonhuman Primates Fed a High-Fat Diet

Endocrinology ◽  
2010 ◽  
Vol 151 (4) ◽  
pp. 1622-1632 ◽  
Author(s):  
B. E. Grayson ◽  
P. R. Levasseur ◽  
S. M. Williams ◽  
M. S. Smith ◽  
D. L. Marks ◽  
...  
Keyword(s):  
Adult Female ◽  
Proinflammatory Cytokines ◽  
Stress Responses ◽  
High Fat Diet ◽  
Maternal Obesity ◽  
High Fat ◽  
Melanocortin System ◽  
Third Trimester ◽  
Local Inflammatory Response ◽  
Obesity And Diabetes

The hypothalamic melanocortin system, which controls appetite and energy expenditure, develops during the third trimester in primates. Thus, maternal nutrition and health may have a profound influence on the development of this system. To study the effects of chronic maternal high-fat diet (HFD) on the development of the melanocortin system in the fetal nonhuman primate, we placed adult female macaques on either a control (CTR) diet or a HFD for up to 4 yr. A subgroup of adult female HFD animals was also switched to CTR diet during the fifth year of the study (diet reversal). Third-trimester fetuses from mothers on HFD showed increases in proopiomelanocortin mRNA expression, whereas agouti-related protein mRNA and peptide levels were decreased in comparison with CTR fetuses. Proinflammatory cytokines, including IL-1β and IL-1 type 1 receptor, and markers of activated microglia were elevated in the hypothalamus, suggesting an activation of the local inflammatory response. Fetuses of diet-reversal mothers had normal melanocortin levels. These results raise the concern that chronic consumption of a HFD during pregnancy, independent of maternal obesity and diabetes, can lead to widespread activation of proinflammatory cytokines that may alter the development of the melanocortin system. The abnormalities in the fetal POMC system, if maintained into the postnatal period, could impact several systems, including body weight homeostasis, stress responses, and cardiovascular function. Indeed, the HFD offspring develop early-onset excess weight gain. These abnormalities may be prevented by healthful nutrient consumption during pregnancy even in obese and severely insulin-resistant individuals.

scholarly journals Mechanisms of Chronic Metabolic Stress in Arrhythmias

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 1012
Author(s):  
Blake H. Gowen ◽  
Michael V. Reyes ◽  
Leroy C. Joseph ◽  
John P. Morrow
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Disease ◽  
Cardiac Arrhythmias ◽  
High Fat Diet ◽  
Metabolic Stress ◽  
Metabolic Changes ◽  
High Fat ◽  
Mechanistic Explanations

Cardiac arrhythmias are responsible for many cardiovascular disease-related deaths worldwide. While arrhythmia pathogenesis is complex, there is increasing evidence for metabolic causes. Obesity, diabetes, and chronically consuming high-fat foods significantly increase the likelihood of developing arrhythmias. Although these correlations are well established, mechanistic explanations connecting a high-fat diet (HFD) to arrhythmogenesis are incomplete, although oxidative stress appears to be critical. This review investigates the metabolic changes that occur in obesity and after HFD. Potential therapies to prevent or treat arrhythmias are discussed, including antioxidants.

scholarly journals Lactational Metformin Treatment in Mouse Dams Ameliorates Maternal High-Fat Diet-induced Metabolic Complications in Male Offspring

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Linh V Nguyen ◽  
Khanh V Doan ◽  
Keyword(s):  
Glucose Tolerance ◽  
Glucose Homeostasis ◽  
High Fat Diet ◽  
Maternal Obesity ◽  
Male Offspring ◽  
Lactation Period ◽  
Metformin Treatment ◽  
High Fat ◽  
Metabolic Complications

Maternal obesity/diabetes severely affects the offspring’s metabolism not only during the fetal and early life development but also later on in the childhood and adulthood stages. Recent evidence suggested that maternal metformin treatment during pregnancy and breastfeeding might provide long-term metabolic benefits on offspring’s glucose homeostasis. We employed a mouse model of maternal overnutrition induced by high fat diet (HFD) to investigate whether an early metformin treatment in mouse dams during lactation period attenuates the maternal HFD-induced metabolic complications in male offspring. The results showed that male offspring from metformin-exposed mothers during suckling period displayed lower body weight and decreased white fat contents. Furthermore, these male offspring had lower blood glucose levels, decreased hyperinsulinemia, enhanced glucose tolerance and insulin sensitivity. Moreover, we found that short-term metformin treatment during lactation period in mouse dams solely improved the glucose tolerance of male offspring exposed with high fat diet (HFD) during both in utero and early postnatal stages, which might primarily result from an increase in insulin secretion. However, this metformin treatment in mouse dams was enabled to abolish most of the metabolic complications of the male offspring exposed with HFD during lactation period. Together, these findings suggest that an early intervention in mouse dams by metformin treatment during lactation period may provide long-term metabolic benefits in regulation of male offspring’s glucose homeostasis.

scholarly journals Parental SIRT1 Overexpression Attenuate Metabolic Disorders Due to Maternal High-Fat Feeding

2020 ◽  
Vol 21 (19) ◽  
pp. 7342
Author(s):  
Long T. Nguyen ◽  
Sonia Saad ◽  
Hui Chen ◽  
Carol A. Pollock
Keyword(s):  
Body Weight ◽  
Stress Responses ◽  
High Fat Diet ◽  
Metabolic Disorders ◽  
Maternal Obesity ◽  
High Fat ◽  
Metabolic Markers ◽  
Lower Body Weight ◽  
Hepatic Glucose ◽  
Fat Feeding

Maternal obesity can contribute to the development of obesity and related metabolic disorders in progeny. Sirtuin (SIRT)1, an essential regulator of metabolism and stress responses, has recently emerged as an important modifying factor of developmental programming. In this study, to elucidate the effects of parental SIRT1 overexpression on offspring mechanism, four experimental groups were included: (1) Chow-fed wild-type (WT)-dam × Chow-fed WT-sire; (2) High-fat diet (HFD)-fed WT-dam × Chow-fed WT-sire; (3) HFD-fed hemizygous SIRT1-transgenic (Tg)-dam × Chow-fed WT-sire; and (4) HFD-fed WT dam × Chow-fed Tg-sire. Our results indicate that Tg breeders had lower body weight and fat mass compared to WT counterparts and gave birth to WT offspring with reductions in body weight, adiposity and hyperlipidaemia compared to those born of WT parents. Maternal SIRT1 overexpression also reversed glucose intolerance, and normalised abnormal fat morphology and the expression of dysregulated lipid metabolism markers, including SIRT1. Despite having persistent hepatic steatosis, offspring born to Tg parents showed an improved balance of hepatic glucose/lipid metabolic markers, as well as reduced levels of inflammatory markers and TGF-β/Smad3 fibrotic signalling. Collectively, the data suggest that parental SIRT1 overexpression can ameliorate adverse metabolic programming effects by maternal obesity.

Sign in / Sign up

Export Citation Format

Share Document